HP is a recently discovered bacteria increasingly being recognized as an etiologic agent for a variety of upper gastrointestinal diseases (see Kim et al., in the American Journal of Clinical Pathology, 1990, volume 94, pages 187 through 191) including gastritis, ulcers, cancer, and associated disorders. In the case of a stomach infection, HP may be identified in the mucus layer adjacent to columnar epithelial cells. In the case of a stomach infection, HP produces a urease enzyme and influences the ammonium levels in the gastro-intestinal tract of the patient.
It has recently been discovered that an ammonium electrode can be used to indicate the presence of HP bacteria in gastric tissue. (See Butcher, et al., in Digestion, 1992, volume 53, pages 142 through 148). However, this discovery was of the use of such an electrode on in vitro (cell cultures in a laboratory) and not in vivo (in a living patient). Biopsies were required, and information was obtained only for the condition present at the time that the biopsy was obtained. No in patient, continuous, real time, ambulatory monitoring was indicated, nor was the possibility of combining such measurements, with simultaneous measurement of other related parameters.
Diagnosis and monitoring of an HP infection can be made in a variety of ways including aspiration, a test for antibodies (serology), and a test of the expiratory gas (mass spectrometry), of the patient. Presently treatment for HP infections often involves use of a combination of drugs including antibiotics and components that directly increase the pH of the gastric juice.
To diagnose and monitor the results of treatment for HP infection, serological methods are now often used. Several ELISA tests are commercially available. However, serological methods may not be optimal, since antibodies may remain the blood for months after an infection is eliminated. Likewise, mass spectrometry of expiration gases may be unsatisfactory because the procedure can be cumbersome to perform and may give false results due to momentary fluctuations in the makeup of such gases. Histology can be a reliable way to detect the presence of HP, but requires a biopsy.
However, the inventor of the present invention has found that, by in vivo intragastro-intestinal monitoring of ammonium levels over a prolonged time period such as an hour or more, the activity of the HP bacteria may be monitored and diagnosed, as well as the results of any treatment thereby immediately and accurately accessed.
It is an object of the present invention to realize a simple system and method, suitable for ambulatory use, that measure intragastrointestinal ammonium concentrations with an intragastrointestinal catheter, over a prolonged period. It is a further object of the present invention to present variations of ammonium concentrations during the various periods of a circadian cycle, such as after meals, during sleep, and so forth. This permits diagnosis and evaluation of treatments for HP infections. Furthermore the invention may be used to simultaneously measure other intragastrointestinal parameters such as potential difference, pH, and motility parameters.
Characteristic of HP is its abundant production of urease. This fact is used in the diagnostic CLO test where a biopsy is put into contact with a urea marked glass plate. Because urease splits urea into carbon dioxide and ammonia with a consequent increase of pH, a pH dependent change in color (to phenol-red) is indicative of the presence of HP. Again, this method has the drawback of an obligatory biopsy.
A non-invasive breath test, presently under development, uses the carbon isotope 13C to mark urea. The marked urea is then administered in liquid form to the patient. If urease is present, then the marked carbon is split off the urea, absorbed into the patient's blood circulation, and finally exhaled as carbon dioxide. The exhaled carbon dioxide can be detected with a mass spectrometer. This is a somewhat cumbersome method as it requires specially marked carbon and an expensive mass spectrometer.